From weather to symptoms: Preliminary links between weather and inflammation in schizophrenia

Negative symptoms in schizophrenia are a major determinant of long-term disability, yet drivers of symptom variability remain poorly understood. Weather-related immune shifts have been proposed as a potential contributing factor, consistent with the immunoseasonal theory.

We conducted an observational cross-sectional study in 81 adults (18-65 years) with schizophrenia assessed across three psychiatric centers between January and October 2025. Negative symptom severity was measured using the PANSS negative subscale (N1-N7). For each assessment, meteorological data from the nearest station were collected and averaged over a 3-day window (the assessment day and the two preceding days): relative humidity, mean temperature, sunshine duration, wind speed, precipitation, and atmospheric pressure. Serum IFN-γ IL-1β, IL-6, IL-7, TNF-α, TNF-β concentrations were assayed. A composite index reflecting general inflammatory response and Th1 activity was derived using principal component analysis (PCA) to explore the assumptions of the immunoseasonal theory. Associations were tested using linear regression, mediation models were additionally explored for cytokines.

Higher relative humidity, lower mean temperature, and longer sunshine duration were associated with greater negative symptom severity. IL-1β, IL-6, IL-7, TNF-α and a General inflammatory component showed a positive association with PANSS-N scores. Relative humidity predicted higher IL-1β and IL-7 levels, whereas no comparable relationship was found for TNF-α. General inflammatory component was also predicted in simplified models. In mediation analyses, the association between humidity and negative symptoms was partially explained by general inflammatory component.

Relative humidity is a candidate meteorological correlate of negative symptom burden in schizophrenia, with general inflammatory markers, rather than Th1-specific activity, demonstrating a statistically consistent mediation effect. Longitudinal studies are needed to confirm directionality and the stability of these associations.